Ex VivoNicotine Stimulation Augments the Efficacy of Human Peripheral Blood Mononuclear Cell-Derived Dendritic Cell Vaccination via Activating Akt-S6 Pathway

作者：Yan Yan Wang, Yi Yang, Xiang You, Xiao Qian Deng, Chun Fang Hu, Cong Zhu, Jun Yao Wang, Jiao Jiao Gu, Yi Nan Wang, Qing Li, Feng Gao · 发表于：Analytical Cellular Pathology · 年份：2015 · DOI：10.1155/2015/741487 · 被引用次数：9 · 研究领域：Immunotherapy and Immune Responses、CAR-T cell therapy research、T-cell and B-cell Immunology

Our previous studies showed that α7 nicotinic acetylcholine receptor (nAchR) agonist nicotine has stimulatory effects on murine bone marrow-derived semimature DCs, but the effect of nicotine on peripheral blood mononuclear cell- (PBMC-) derived human semimature dendritic cells (hu-imDCs) is still to be clarified. In the present study, hu-imDCs (cultured 4 days) were conferred with ex vivo lower dose nicotine stimulation and the effect of nicotine on surface molecules expression, the ability of cross-presentation, DCs-mediated PBMC priming, and activated signaling pathways were determined. We could demonstrate that the treatment with nicotine resulted in increased surface molecules expression, enhanced hu-imDCs-mediated PBMC proliferation, upregulated release of IL-12 in the supernatant of cocultured DCs-PBMC, and augmented phosphorylation of Akt and ribosomal protein S6. Nicotine associated with traces of LPS efficiently enhanced endosomal translocation of internalized ovalbumin (OVA) and increased TAP-OVA colocalization. Importantly, the upregulation of nicotine-increased surface molecules upregulation was significantly abrogated by the inhibition of Akt kinase. These findings demonstrate that ex vivo nicotine stimulation augments hu-imDCs surface molecules expression via Akt-S6 pathway, combined with increased Ag-presentation result in augmented efficacy of DCs-mediated PBMC proliferation and Th1 polarization.